Lack of orally induced systemic unresponsiveness in IFN-gamma knockout mice.
Splenic T cells isolated from BALB/c mice that had been mucosally tolerized by oral administration of 25 mg of OVA revealed selective increases in IFN-gamma production with impaired levels of IL-2, IL-4, IL-5, and IL-10. These mice possessed reduced splenic OVA-specific T cell proliferative and delayed-type hypersensitivity responses when compared with nontolerized controls. Further, OVA-specific IgG Ab responses in serum and the numbers of IgG Ab-forming cells in spleen were significantly diminished following systemic challenge with OVA in CFA. When IFN-gamma-deficient (IFN-gamma-/-) mice of the same genetic background were given an oral dose of 25 mg of OVA before systemic immunization, no reduction in OVA-specific IgG Ab responses in serum and spleen was seen. Furthermore, the serum IgG Ab responses were restricted to IgG1 and IgG2b subclasses. Interestingly, although IFN-gamma-/- mice displayed a partial diminution of T cell proliferative and delayed-type hypersensitivity responses to OVA, significant responses were still present when compared with the low responses noted in IFN-gamma+/+ mice. In addition, OVA-specific T cells from IFN-gamma-/- mice produced Th2-type cytokines (e.g., IL-4), which provided help for systemic OVA-specific serum IgG1 and IgG2b Ab responses. These findings clearly indicate a central role for IFN-gamma in the induction and maintenance of mucosally induced tolerance.
Kweon
M N
MN
Department of Oral Biology, The Immunobiology Vaccine Center, University of Alabama at Birmingham 35294, USA.
Fujihashi
K
K
VanCott
J L
JL
Higuchi
K
K
Yamamoto
M
M
McGhee
J R
JR
Kiyono
H
H
D000284:Administration, Oral; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D007108:Immune Tolerance / Q000235:genetics*; D018928:Immunity, Mucosal / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D007371:Interferon-gamma / Q000172:deficiency* / Q000235:genetics* / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D007074:Immunoglobulin G; D007371:Interferon-gamma; D010047:Ovalbumin